The purpose of this research proposal is to gain insight into the mechanisms for recovery from vaccinia virus infection. In this way a broader insight into the relationship of the major immune mechanisms to viral replication may be gained. Serum antibody, delayed-type hypersensitivity and non-specific (principally interferon) immune mechanisms are stimulated in the normal individual by vaccinia virus. A model for vaccinia virus infection has been developed in the Rhesus monkey and immune integrity abrogated by X-irradiation and treatment with antilymphocyte serum resulting in a progressive, lethal infection. It is the purpose of this proposed investigation to study the model developed with a view to developing it further and to extracting the relationships indicated above. A secondary, but equally important purpose, is to utilize the model to test various therapeutic regimens currently in use in human medicine designed to counteract the effect of excessive viral replication.